Next Article in Journal
Center of Biomedical Research Excellence in Matrix Biology: Building Research Infrastructure, Supporting Young Researchers, and Fostering Collaboration
Previous Article in Journal
Pioglitazone and Deoxyribonucleoside Combination Treatment Increases Mitochondrial Respiratory Capacity in m.3243A>G MELAS Cybrid Cells
Open AccessArticle

Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration

1
Laboratory of Translational Psychiatry and Focus Program Translational Neurosciences, Johannes Gutenberg University Medical Center Mainz, 55128 Mainz, Germany
2
Institute of Physiological Chemistry, Johannes Gutenberg University Medical Center Mainz, 55128 Mainz, Germany
3
Leibniz Institute for Resilience Research, 55131 Mainz, Germany
4
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark
*
Author to whom correspondence should be addressed.
These authors contribute equally to this work.
These authors shared last authorship.
Int. J. Mol. Sci. 2020, 21(6), 2142; https://doi.org/10.3390/ijms21062142
Received: 31 January 2020 / Revised: 13 March 2020 / Accepted: 17 March 2020 / Published: 20 March 2020
(This article belongs to the Section Molecular Neurobiology)
Background: Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents. Methods: We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg kg−1) or (2R,6R)-HNK (10 mg kg−1). We performed a comprehensive behavioral test battery to characterize the Arc-CreERT2 × CAG-Sun1/sfGFP mouse line which enables targeted recombination in active populations. We performed a molecular study in Arc-CreERT2 × CAG-Sun1/sfGFP female mice using both immunohistochemistry and in situ hybridization. Results: Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in sociability and anxiety tests. Moreover, ketamine and (2R,6R)-HNK had opposite effects in the forced swim test (FST) depending on gender. In addition, in male mice, ketamine-treated animals were less immobile compared to (2R,6R)-HNK, thus showing a different profile of the two drugs in the FST. At the molecular level we identified Bdnf mRNA level to be increased after ketamine treatment in female mice. Conclusion: Arc-CreERT2 × CAG-Sun1/sfGFP mice showed sex differences in social and anxiety behavior and a different pattern between ketamine and (2R,6R)-HNK in the FST in male and female mice. At the molecular level, female mice treated with ketamine showed an increase of Bdnf mRNA level, as previously observed in male mice. View Full-Text
Keywords: ketamine; hydroxynorketamine; antidepressant; rapid-acting; sex difference; BDNF; activated neurons; behavior ketamine; hydroxynorketamine; antidepressant; rapid-acting; sex difference; BDNF; activated neurons; behavior
Show Figures

Figure 1

MDPI and ACS Style

Herzog, D.P.; Mellema, R.M.; Remmers, F.; Lutz, B.; Müller, M.B.; Treccani, G. Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration. Int. J. Mol. Sci. 2020, 21, 2142. https://doi.org/10.3390/ijms21062142

AMA Style

Herzog DP, Mellema RM, Remmers F, Lutz B, Müller MB, Treccani G. Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration. International Journal of Molecular Sciences. 2020; 21(6):2142. https://doi.org/10.3390/ijms21062142

Chicago/Turabian Style

Herzog, David P.; Mellema, Ratnadevi M.; Remmers, Floortje; Lutz, Beat; Müller, Marianne B.; Treccani, Giulia. 2020. "Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration" Int. J. Mol. Sci. 21, no. 6: 2142. https://doi.org/10.3390/ijms21062142

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop